Many of the basic physiological actions of growth hormone- releasing hormone (GHRH) have been investigated since its discovery approximately three years ago. Yet the use of GHRH to enhance growth in humans and other species, while successful and very exciting, has proven to be very laborious and at present holds little practical application. This situation can be greatly improved by developing a clear understanding of the basic mechanisms regulating the secretion of GHRH and which factors impinge on its actions. The experiments proposed in this grant are designed to investigate many of these aspects.
Specific aims are 1) to establish the participating factors involved in the regulation of GHRH and somatostatin secretion, 2) to establish the role and significance of adrenal and gonadal steroids and thyroid hormone on the GHRH-GH neuroendocrine pathways, 3) evaluate the biological activity of agonists and antagonists of GHRH in vivo and 4) evaluate the metabolism of these GHRH analogues and GHRH itself.
These aims will be attained using a variety of in vivo methods. Specifically cerebral spinal fluid collection and hypothalamic-hypophyseal portal blood collection will be used to investigate the mechanisms involved in regulating hypothalamic GHRH and somatostatin secretion. The metabolism of GHRH and how steroid and thyroid hormones modulate the actions of GHRH will be investigated using conscious, freely- moving rats prepared with indwelling venous catheters. The development of a basic knowledge and understanding of the fundamental relationships between GHRH, somatostatin and GH will facilitate the successful use of GHRH on a clinical level to treat growth hormone related disorders and on an agricultural level to enhance growth and foodstuffs utilization. These activities are consistent with my long-term objectives to characterize the physiological relationship between GHRH and GH as it relates to normal growth and development. These objectives range from the neuronal level, e.g., establishing which central nervous system pathways are involved in regulating GHRH secretion, to the environmental level, e.g., establishing the role of GHRH and GH during the period of catch-up growth which occurs following the removal of animals from a food deprivation environment.
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